Dynamic interreceptor coupling: a novel working mechanism of two-dimensional
ryanodine receptor array.
Biophys. J., 92 (4):
1215--1223 (February 2007)DOI: 10.1529/biophysj.106.090670
Abstract
Ryanodine receptors (RyRs) usually form two-dimensional regular array
in sarcoplasmic reticulum membranes in muscle cells. The inter-RyRs
coupling may be essential for the maintenance of quiescent Ca$^2+$
release in resting state, as well as for the coordinated activation
and rapid termination of RyR-mediated Ca$^2+$ release during
excitation-contraction coupling. In our previous work, we have reported
that the inter-RyRs interaction is modulated by RyR channel's functional
state, which inspired us to propose a novel working mechanism of
RyR array: "dynamic inter-RyR coupling". In this work, we built a
simple model based on cellular automata and the Monte-Carlo method
to quantitatively investigate the roles of intermolecular coupling
and its modulation in regulating the signaling capabilities of RyR
array. Our simulation results showed that with a suitable inter-RyR
coupling strength, the combination of rest stability and high response
efficiency, namely optimal signal/noise ratio, of Ca$^2+$ signaling
could be achieved. Moreover, we also found the continued coupling
between open RyRs would delay the system termination rate. The coacquisition
of robust termination of array opening relied on the proper decrease
of coupling strength between activated RyRs. Obviously, such temporally
asymmetric coupling would simultaneously endow the system with physiologically
relevant resting stability and fast termination.
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